Human T-cell leukemia virus Type 1 (HTLV-I) is associated with malignant adult T-cell leukemia (ATL) and has recently been linked to two degenerative neurologic diseases, HTLV-I associated myelopathy and multiple sclerosis. Viral replication is dependent upon the viral Tax protein, which transcriptionally activates the HTLV-I LTR and can also activate cellular and other viral promoters. The ability of HTLV-I to induce malignant transformation of cultured cells also requires a functional Tax gene.
Transcriptional activation of the HTLV-I LTR by Tax involves three 21 bp repeats, referred to as Tax-response elements (TRE). Mutational analysis indicated that the critical region of each 21 bp repeat is an ATF binding site. ATF proteins (ATFs) are a family of cellular transcription factors that contain homologous basic region/leucine zipper DNA binding (bZIP) domains. Several ATFs have been shown to bind to TRE sequences. These and other observations suggest that Tax, which is not a sequence-specific DNA binding protein, functions through ATFs to stimulate transcription.